Method of maintaining the function of liver tissue cells over long time

Abstract

The function of liver tissue cells can be maintained over a long period of time by culturing the liver tissue cells on a cell culture support, which is coated with a polymer showing a change in the hydration force in the temperature range of from 0 to 80° C., within the temperature range wherein the polymer has a small hydration force, then changing the temperature of the liquid culture medium to a level at which the polymer shows a large hydration force, thus stripping off the liver tissue cells having been cultured, and transplanting the thus obtained liver tissue cells into a definite site in vivo.

1 . A method of maintaining the function of liver tissue cells over a long period of time comprising culturing liver tissue cells on a cell culture support whose surface is coated with a polymer which shows a change in the hydration force in the temperature range of 0 to 80° C. within the temperature range where the hydration force of the polymer is weak, thereafter changing the temperature of the liquid culture medium to a level at which the hydration force of the polymer becomes strong to peel cultured liver tissue cells, and then transplanting the obtained liver tissue cells into a definite site in the living body of an animal including a human. 
     
     
         2 . The method of maintaining the function of hepatic tissue cells over a long period of time of  claim 1 , wherein the peeled hepatic tissue cells are in the form of a sheet. 
     
     
         3 . The method of maintaining the function of hepatic tissue cells over a long period of time of  claim 2 , wherein the peeled hepatic tissue cells are in the form of a laminate. 
     
     
         4 . (canceled) 
     
     
         5 . The method of maintaining the function of hepatic tissue cells over a long period of time of  claim 1 , wherein on completion of culturing, the cultured hepatic tissue cells are allowed to adhere to a carrier and are peeled together with the carrier as the peeling method. 
     
     
         6 . The method of maintaining the function of hepatic tissue veils over a long period of time of  claim 1 , wherein the site to be transplanted is subcutaneous tissue, intraperitoneal tissue, the liver or a muscle within the living body. 
     
     
         7 . The method of maintaining the function of hepatic tissue cells over a long period of time of  claim 1 , wherein the site to be transplanted is previously provided with the induction of angiogenesis. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . An artificial liver utilizing the method of maintaining the function of hepatic tissue cells over a long period of time of  claim 1 . 
     
     
         13 . (canceled) 
     
     
         14 . The artificial liver of  claim 12  having an object to treat hepatic enzyme deficiency, hemophilia, coagulopathy, liver failure, fulminant hepatitis, chronic hepatitis, liver cirrhosis, a liver resected patient and an infectious disease or to assist the function of the liver. 
     
     
         15 . The artificial liver of  claim 12  which produces human blood coagulation factor VIII and/or human blood coagulation factor IX. 
     
     
         16 . (canceled) 
     
     
         17 . An animal other than a human transplanted with hepatic tissue cells utilizing the method of maintaining the. function of hepatic tissue cells over a long period of time of  claim 1 . 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . A system of evaluating the function of the liver comprising administering a test substance to an animal transplanted with hepatic tissue cells obtained by the method of  claim 17  and judging the influence of the test substance on the function of the liver. 
     
     
         21 . A method for producing liver tissue cells for transplantation which enables long-term maintenance of the function of hepatic tissue cells comprising culturing liver tissue cells on a cell culture support whose surface is coated with a polymer which changes in the hydration force in the temperature range of 0 to 80° C. within the temperature range where the hydration force of the polymer is weak and thereafter changing the temperature of the liquid culture medium to a level at which the hydration force of the polymer becomes strong to peel the cultured hepatic tissue cells. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . An artificial liver utilizing the method for producing liver tissue cells for transplantation which enables long-term maintenance of the function of hepatic tissue cells of  claim 21 . 
     
     
         33 . (canceled) 
     
     
         34 . The artificial liver of  claim 32  having an object to treat hepatic enzyme deficiency, hemophilia, coagulopathy, liver failure˜fulminant hepatitis. chronic hepatitis, liver cirrhosis, a liver resected patient and an infectious disease or to assist the function of the liver. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . An animal other than a human transplanted with hepatic tissue cells utilizing the method of maintaining the function of hepatic tissue cells over a long period of time of  claim 21 . 
     
     
         38 . (canceled) 
     
     
         39 . (canceled)